The control of membrane conductance by nicotinic acetylcholine receptors is studied. At myoneural junctions and electroplaques, the conductance produced by a steady concentration of agonist varies with the transmembrane potential. Potential therefore provides a tool for probing different states of the acetylcholine receptor. Techniques will include voltage-clamp and membrane noise experiments. Temperature, local anesthetics, internal and external ions, and different agonists are expected to influence receptor states. In a suspension of membrane-bound vesicles, the conductance of the suspension increases with that of the membranes. Based on this fact, a simple and precise assay will be developed for studying cholinergic excitation with receptor-rich vesicles from Torpedo electric organ. Dose-effect curves for agonists, as influenced by many of the agents listed above, will be investigated with the goal of developing a model for the activation of receptors. The studies will extend to vesicles reconstituted from pure acetylcholine receptors and lipids. The present approaches may prove generally useful for investigating the effects of transmitters, hormones, and drugs on membrane ionic permeability. BIBLIOGRAPHIC REFERENCES: Lester, H.A., J.-P. Changeux, and R.E. Sheridan. Conductance increases produced by bath application of cholinergic agonists to Electrophorus electroplaques. J. Gen. Physiol. 65: 797-816 (1975). Sheridan, R. E. and H.A. Lester. Relaxation spectroscopy of the acetylcholine receptor: responses to voltage jumps in isolated Electrophorus electroplaques. Biophys. Soc. Abst. 268a (1975).